nach oben

Erschienen in:

01.12.2012 | Original Article

Intrapulmonary Shear Stress Enhancement: A New Therapeutic Approach in Pulmonary Arterial Hypertension

verfasst von: Sayed Nour, Gang Dai, Daniel Carbognani, Minze Feng, Daya Yang, Nermine Lila, Juan Carlos Chachques, Guifu Wu

Erschienen in: Pediatric Cardiology | Ausgabe 8/2012

Einloggen, um Zugang zu erhalten

Abstract

Objective

Pulmonary arterial hypertension (PAH) is a dysfunctional endothelium disease with increased pulmonary vascular resistance (PVR) and poor prognosis. Current therapies are still insufficient. Here we propose a new pulsatile device as a more effective tool for PAH management compared with traditional treatments.

Materials and Methods

Twelve piglets (10.3 ± 3.8 kg) were given either intrapulmonary pulsatile [P (n = 6)] or nonpulsatile [NP (n = 6)] tadalafil treatment. After median sternotomy and heparin injection (250 IU/kg), both groups underwent aorto-pulmonary surgical shunt for 1 h. During a second 1 h period in group P, a catheter prototype, driven by a small ventilator, was introduced into the pulmonary trunk and pulsated intermittently at 110 bpm irrespective of heart rate (90.6 ± 10.74 bpm). In group NP, tadalafil was given orally (1 mg/kg).

Results

Hemodynamics and cardiac output (CO) were significantly (p < 0.05) improved in group P compared with group NP: CO was 0.56 ± 0.0.26 versus 0.54 ± 0.11 (L/min), respectively. Mean pulmonary artery pressure (PAP) was decreased in group P compared with group NP: PAP was 9.6 ± 2.97 versus 32.2 ± 5.07, respectively. Vascular resistances (dynes.s.cm⁻⁵/kg) were significantly lower in group P versus group NP: pulmonary resistance was 85 ± 42.12 versus 478 ± 192.91 and systemic resistance was 298.8 ± 172.85 versus 1301 ± 615.79, respectively. Using Western blot analysis, endogenous NO synthase expression in PA segments was nonsignificantly (p > 0.05) greater in group P (0.81 ± 0.78) versus (0.62 ± 0.35) group NP.

Conclusion

Induced with an appropriate device, intrapulmonary shear stress–mediated endothelial function enhancement provides a more effective nearly physiological therapy for PAH.

Schannwell CM, Steiner S, Strauer BE (2007) Diagnostics in pulmonary hypertension. J Physiol Pharmacol 58(Suppl 5 Pt 2):591–602PubMed

Simonneau G, Robbins IM, Beghetti M, Channick RN, Delcroix M, Denton CP et al (2009) Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 54:43–54CrossRef

Humbert M, Morrell NW, Archer SL (2004) Cellular and molecular pathobiology of pulmonary arterial hypertension. J Am Coll Cardiol 43:13–24CrossRef

Felker GM, Thompson RE, Hare JM, Hruban RH, Clemetson DE, Howard DL et al (2000) Underlying causes and long-term survival in patients with initially unexplained cardiomyopathy. N Engl J Med 342:1077–1084PubMedCrossRef

Boutet K, Montani D, Jaïs X (2008) Review: therapeutic advances in pulmonary arterial hypertension. Ther Adv Respir Dis 2:249–265PubMedCrossRef

Checchia PA, Bronicki RA, Goldstein B (2012) Review of inhaled nitric oxide in the pediatric cardiac surgery setting. Pediatr Card [Epub Ahead of Print]

Tessler RB, Zadinello M, Fiori H, Colvero M, Belik J, Fiori RM (2008) Tadalafil improves oxygenation in a model of newborn pulmonary hypertension. Pediatr Crit Care Med 9:330–332PubMedCrossRef

Nemoto S, Sasaki T, Ozawa H, Katsumata T, Okumura K et al (2010) Oral sildenafil for persistent pulmonary hypertension early after congenital cardiac surgery in children. Eur J Cardiothorac Surg 38:71–77PubMedCrossRef

McLaughlin VV, Benza RL, Rubin LJ, Channick RN, Voswinckel R, Tapson VF et al (2010) Addition of inhaled treprostinil to oral therapy for pulmonary arterial hypertension: a randomized controlled clinical trial. J Am Coll Cardiol 55:1915–1922PubMedCrossRef

10.

Nef HM, Möllmann H, Hamm C (2010) Pulmonary hypertension: updated classification and management of pulmonary hypertension. Heart 96:552–559PubMedCrossRef

11.

Macchia A, Marchioli R, Marfisi R (2007) A meta-analysis of trials of pulmonary hypertension: a clinical condition looking for drugs and research methodology. Am Heart J 153:1037–1047PubMedCrossRef

12.

Bush A (2006) Pulmonary and critical care updates (update in pediatrics 2005). Am J Respir Crit Care Med 173:585–592PubMedCrossRef

13.

Oishi P, Grobe A, Benavidez E (2006) Inhaled nitric oxide induced NOS inhibition and rebound pulmonary hypertension: a role for superoxide and peroxynitrite in the intact lamb. Am J Physiol Lung Cell Mol Physiol 290:L359–L366PubMedCrossRef

14.

Miller OI, Tang SF, Keech A, Celermajer DS (1995) Rebound pulmonary hypertension on withdrawal from inhaled nitric oxide [letter]. Lancet 346:51–52PubMedCrossRef

15.

Segal ES, Valette C, Oster L (2005) Risk management strategies in the postmarketing period: safety experience with the US and European Bosentan Surveillance Programmes. Drug Saf 28:971–980PubMedCrossRef

16.

Stevens T (2008) Lung vascular cell heterogeneity: endothelium, smooth muscle, and fibroblasts. Proc Am Thorac Soc 5:783–791PubMedCrossRef

17.

Khambadkone S, Li J, de Leval MR, Cullen S, Deanfield JE, Redington AN (2003) Basal pulmonary vascular resistance and nitric oxide responsiveness late after Fontan-type operation. Circulation 107:3204–3208PubMedCrossRef

18.

Handoko ML, de Man FS, Allaart CP, Paulus WJ, Westerhof N, Vonk-Noordegraaf A (2010) Perspectives on novel therapeutic strategies for right heart failure in pulmonary arterial hypertension: lessons from the left heart. Eur Respir Rev 19:72–82PubMedCrossRef

19.

Aaron CP, Tandri H, Barr RG, Johnson WC, Bagiella E, Chahal H (2011) Physical activity and right ventricular structure and function. The MESA Right Ventricle Study. Am J Respir Crit Care Med 183:396–404PubMedCrossRef

20.

Olufsen MS, Nadim A (2004) On deriving lumped models for blood flow and pressure in the systemic arteries. Math Biosci Eng 1:61–80PubMedCrossRef

21.

Roselli RJ, Brophy SP (2003) Redesigning a biomechanics course using challenge-based instruction. IEEE Eng Med Biol Mag 22:66–70PubMedCrossRef

22.

Gonzales-Luis G, Fletcher AJ, Moreno L (2007) Nitric oxide-mediated nonadrenergic noncholinergic relaxation of piglet pulmonary arteries decreases with postnatal age. J Physiol Pharmacol 58:45–56PubMed

23.

Furchgott RF, Zawadzki JV (1980) The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288:373–376PubMedCrossRef

24.

Vallance P, Collier J, Moncada S (1989) Effects of endothelium-derived nitric oxide on peripheral arteriolar tone in man. Lancet 2:997–1000PubMedCrossRef

25.

Bloch KD, Ichinose F, Roberts JD Jr, Zapol WM (2007) Inhaled NO as a therapeutic agent. Cardiovasc Res 75:339–348PubMedCrossRef

26.

Levin YD, White RJ (2011) Novel therapeutic approaches in pulmonary arterial hypertension: focus on tadalafil. Drugs Today (Barc) 47:145–156

27.

de Carvalho AC, Hovnanian AL, Fernandes CJ, Lapa M, Jardim C, Souza R (2006) Tadalafil as treatment for idiopathic pulmonary arterial hypertension. Arq Bras Cardiol 87:e195–e197PubMedCrossRef

28.

Thomas DD, Liu X, Kantrow SP (2001) The biological lifetime of nitric oxide: implications for the perivascular dynamics of NO and O2. Proc Natl Acad Sci USA 98:355–360PubMedCrossRef

29.

Neri Serneri GG (1981) Pathophysiological aspects of platelet aggregation in relation to blood flow rheology in microcirculation. Ric Clin Lab 11:39–46PubMed

30.

Nour S, Wu G, Zhensheng Z, Chachques JC, Carpentier A, Payen D (2009) The forgotten driving forces in right heart failure: new concept and device. Asian Cardiovasc Thorac Ann 17:525–530PubMed

31.

Fourie PR, Coetzee AR, Bolliger CT (1992) Pulmonary artery compliance: its role in right ventricular-arterial coupling. Cardiovasc Res 26:839–844PubMedCrossRef

32.

Kitamura N, Miki T, Fukushima Y, Yamaguchi A, Otaki M, Minoji T (1988) Expanding the surgical indication to the cases with high risk valve diseases. Nihon Geka Gakkai Zasshi 89:1446–1449PubMed

33.

Letsou GV, Franco KL, Detmer W (1993) Pulmonary artery balloon counterpulsation: safe after peripheral placement. Ann Thorac Surg 55:741–746PubMedCrossRef

34.

Beghetti M, Tissot C (2009) Pulmonary arterial hypertension in congenital heart diseases. Semin Respir Crit Care Med 30:421–428PubMedCrossRef

35.

Galie N, Manes A, Palazzini M, Negro L, Marinelli A, Gambetti S (2008) Management of pulmonary arterial hypertension associated with congenital systemic-to-pulmonary shunts and Eisenmenger’s syndrome. Drugs 68:1049–1066PubMedCrossRef

36.

Motwani JG, Topol EJ (1998) Aortocoronary saphenous vein graft disease: pathogenesis, predisposition, and prevention. Circulation 97:916–931PubMedCrossRef

37.

Dimopoulos K, Peset A, Gatzoulis MA (2008) Evaluating operability in adults with congenital heart disease and the role of pretreatment with targeted pulmonary arterial hypertension therapy. Int J Cardiol 129:163–171PubMedCrossRef

38.

Pyxaras SA, Pinamonti B, Barbati G, Santangelo S, Valentincic M, Cettolo F et al (2011) Echocardiographic evaluation of systolic and mean pulmonary artery pressure in the follow-up of patients with pulmonary hypertension. Eur J Echocardiogr 12:696–701PubMedCrossRef

39.

Smadja DM, Gaussem P, Mauge L, Israël-Biet D, Dignat-George F, Peyrard S et al (2009) Circulating endothelial cells: a new candidate biomarker of irreversible pulmonary hypertension secondary to congenital heart disease. Circulation 119:374–381PubMedCrossRef

40.

Mavroudis C, Backer CL, Kohr LM, Deal BJ, Stinios J, Muster AJ et al (1999) Bidirectional Glenn shunt in association with congenital heart repairs: the 1(1/2) ventricular repair. Ann Thorac Surg 68:976–981PubMedCrossRef

41.

Nour S (2012) Flow and rate: concept and clinical applications of a new hemodynamic theory. In: Misra AN (ed) Biophysics. Intech, Rijeka, pp 17–76

42.

Ochoa CD, Wu S, Stevens T (2010) New developments in lung endothelial heterogeneity: Von Willebrand factor, P-selectin, and the Weibel-Palade body. Semin Thromb Hemost 36:301–308PubMedCrossRef

43.

Scholz KH (1999) Reperfusion therapy and mechanical circulatory support in patients in cardiogenic shock. Herz 24:448–464PubMedCrossRef

44.

Nour S, Dai G, Wang Q, Wang F, Chachques JC, Wu GF (2012) The forgotten driving forces in right heart failure: Preclinical experimental study. Asian Cardiovasc Thorac Ann doi:10.1177/0123456789123456

45.

Thomas M (2008) Management of pulmonary hypertension in the intensive care unit. Crit Care Med 36:651–652PubMedCrossRef

46.

Zamanian RT, Haddad F, Doyle RL, Weinacker AB (2007) Management strategies for patients with pulmonary hypertension in the intensive care unit. Crit Care Med 35:2037–2050PubMedCrossRef

47.

Robbins IM (2004) Advancing therapy for pulmonary arterial hypertension: can animal models help? Am J Respir Crit Care Med 169:5–6PubMedCrossRef

48.

Bauer NR, Moore TM, McMurtry IF (2007) Rodent models of PAH: are we there yet? Am J Physiol Lung Cell Mol Physiol 293:580–582CrossRef

49.

Ghorishi Z, Milstein JM, Poulain FR, Moon-Grady A, Tacy T, Bennett SH et al (2007) Shear stress paradigm for perinatal fractal arterial network remodeling in lambs with pulmonary hypertension and increased pulmonary blood flow. Am J Physiol Heart Circ Physiol 292:3006–3018CrossRef

50.

Stenbøg EV, Steinbrüchel DA, Thomsen AB, Baandrup U, Heickendorff L et al (2001) The pulmonary vasculature in a neonatal porcine model with increased pulmonary blood flow and pressure. Cardiol Young 11:420–430PubMedCrossRef

51.

Clark EB (1987) Mechanisms in the pathogenesis of congenital cardiac malformations. In: Pierpont MEM, Moller JH (eds) The genetics of cardiovascular disease. Nijhoff Publishing, Boston, pp 3–11CrossRef

52.

Taylor MB, Laussen PC (2010) Fundamentals of management of acute postoperative pulmonary hypertension. Pediatr Crit Med 11:27CrossRef

53.

Martin J, Siegenthaler MP, Friesewinkel O (2004) Implantable left ventricular assist device for treatment of pulmonary hypertension in candidates for orthotopic heart transplantation—a preliminary study. Eur J Cardiothorac Surg 25:971–977PubMedCrossRef

54.

Wilmot I, Morales DL, Price JF (2011) Effectiveness of mechanical circulatory support in children with acute fulminant and persistent myocarditis. J Card Fail 17:487–494PubMedCrossRef

55.

Pihkala J, Yazaki S, Mehta R, Lee KJ, Chaturvedi R, McCrindle BW et al (2007) Feasibility and clinical impact of transcatheter closure of interatrial communications after a fenestrated Fontan procedure: medium-term outcomes. Catheter Cardiovasc Interv 69:1007–1014PubMedCrossRef

56.

Falase B, Easaw J, Youhana A (2001) The role of nicorandil in the treatment of myocardial ischaemia. Expert Opin Pharmacother 2:845–856PubMedCrossRef

Titel: Intrapulmonary Shear Stress Enhancement: A New Therapeutic Approach in Pulmonary Arterial Hypertension
verfasst von: Sayed Nour
Gang Dai
Daniel Carbognani
Minze Feng
Daya Yang
Nermine Lila
Juan Carlos Chachques
Guifu Wu
Publikationsdatum: 01.12.2012
Verlag: Springer-Verlag
Erschienen in: Pediatric Cardiology / Ausgabe 8/2012
Print ISSN: 0172-0643
Elektronische ISSN: 1432-1971
DOI: https://doi.org/10.1007/s00246-012-0322-8

Neu im Fachgebiet Kardiologie

16.04.2024 | Chronische Herzinsuffizienz | Nachrichten

Update Kardiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Intrapulmonary Shear Stress Enhancement: A New Therapeutic Approach in Pulmonary Arterial Hypertension

Abstract

Objective

Materials and Methods

Results

Conclusion

Neu im Fachgebiet Kardiologie

Sind Betablocker auch für ältere herzschwache Personen nützlich?

Stillende Frauen haben geringeres kardiovaskuläres Risiko

Selbstexpandierende TAVI-Klappen bei kleinem Aortenanulus im Vorteil

Verbesserung der HDL-Funktion als Lipidtherapie floppt in Mega-Studie

Update Kardiologie

Springer Medizin

Abstract

Objective

Materials and Methods

Results

Conclusion

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 8/2012

Prenatal Evaluation and Management of Fetuses Exposed to Anti-SSA/Ro Antibodies

John Hunter (1728–1793) and the Earliest Description of a Double Superior Vena Cava and Isolation of the Left Subclavian Artery

Children With Protein-Losing Enteropathy After the Fontan Operation Are at Risk for Abnormal Bone Mineral Density

Large Right Ventricular Fibroma in a 6-Month-Old Infant

Novel Postoperative Use of Beta-Blocking Medication for Infants With Left Ventricular Outflow Obstruction and Diastolic Myocardial Dysfunction

Short-Term Result of Ductus Arteriosus Stent Implantation Compared With Surgically Created Shunts

Neu im Fachgebiet Kardiologie

Sind Betablocker auch für ältere herzschwache Personen nützlich?

Stillende Frauen haben geringeres kardiovaskuläres Risiko

Selbstexpandierende TAVI-Klappen bei kleinem Aortenanulus im Vorteil

Verbesserung der HDL-Funktion als Lipidtherapie floppt in Mega-Studie

Update Kardiologie